盐酸罗匹尼罗渗透泵型控释片的药代动力学研究

摘要

Objective To establish a determination method of ropinirole hydrochloride in animal plasma to evaluate the pharmacoki‐netics of controlled release Ropinirole Hydrochloride Osmotic Pump Tablets ,and to provide the relative bioavailability compared with reference formulation (Requip XL ) Methods A single oral dose of controlled release Ropinirole Hydrochloride Osmotic Pump Tablets (test formulation) and Requip XL (reference formulation) were administered to six Beagle dogs respectively .The concentration of ropinirole hydrochloride in Beagle dog plasma was analyzed by LC‐MS .The pharmacokinetic parameters and rela‐tive bioavailability were calculated .Results The main pharmacokinetic parameters of reference formulation and tested formulation were as follows :tmax were (2 .92 ± 0 .49) and (3 .58 ± 0 .49) h ,respectively ;Cmax were (2 .60 ± 0 .41) and (2 .35 ± 0 .39) ng · mL -1 ,respectively ;MRT were (7 .76 ± 0 .89) and (8 .48 ± 0 .59) h ,respectively ;t1/2 (Ke) were (4 .70 ± 0 .67) and (5 .94 ± 1 .19) h , respectively ;AUC(0‐t) were (16 .06 ± 5 .55) and (17 .90 ± 2 .75) ng · mL -1 · h ,respectively ;AUC(0 - ∞ ) were (16 .71 ± 5 .87) and (19 .03 ± 3 .08) ng · mL -1 · h ,respectively .The relative bioavailability of the test formulation and reference formulation was 111 .48% .Conclusion The results suggested that the main pharmacokinetic parameters have no significant difference .The meth‐od established can be used to determine the concentration of ropinirole hydrochloride in plasma and to evaluate the pharmacokinet‐ics and relative bioavailability in animal studies .%目的：建立一种测定动物血浆中盐酸罗匹尼罗的方法，并进行盐酸罗匹尼罗渗透泵型控释片的药物动力学研究，并计算与参比制剂（RequipXL）的相对生物利用度。方法6只Beagle犬分别单次口服盐酸罗匹尼罗渗透泵片（受试制剂）和Requip XL （参比制剂）1片，用LC‐M S法测定血浆中的药物浓度，计算药物动力学参数和相对生物利用度。结果参比制剂和受试制剂的主要药代动力学参数 tmax分别为（2．92±0．49）和（3．58±0．49）h ，Cmax分别为（2．60±0．41）和（2．35±0．39） ng · mL －1，MRT分别为（7．76±0．89）和（8．48±0．59） h ，t1／2（Ke）分别为（4．70±0．67）和（5．94±1．19） h ，AUC（0～ t）分别为（16．06±5．55）和（17．90±2．75） ng · mL －1· h ，AUC（0～∞）分别为（16．71±5．87）和（19．03±3．08） ng · mL －1· h ，受试制剂相对于参比制剂的相对生物利用度 Fr 为111．48％。结论统计结果显示，各主要药动学参数均无显著性差异。本方法能测定口服盐酸罗匹尼罗渗透泵的血药浓度，进行动物药物动力学和相对生物利用度研究。